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pmid:20459635
Predicting environmental chemical factors associated with disease-related gene expression data.
Chirag J Patel · Atul J Butte
BMC medical genomics · 2010 doi:10.1186/1755-8794-3-17
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Our knowledge regarding environment and gene interactions is growing, but frameworks to build an association between gene-environment interactions and disease using preexisting, publicly available data has been lacking. Integrating freely-available environment-gene interaction and disease phenotype data would allow hypothesis generation for potential environmental associations to disease.\nMETHODS: We integrated publicly available disease-specific gene expression microarray data and curated chemical-gene interaction data to systematically predict environmental chemicals associated with disease. We derived chemical-gene signatures for 1,338 chemical/environmental chemicals from the Comparative Toxicogenomics Database (CTD). We associated these chemical-gene signatures with differentially expressed genes from datasets found in the Gene Expression Omnibus (GEO) through an enrichment test.\nRESULTS: We were able to verify our analytic method by accurately identifying chemicals applied to samples and cell lines. 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We downloaded the knowledge-base spanning 4,078 chemicals and 15 461 genes and 85 937 relationships between them in January 2009.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM63205", "GSM63206", "GSM63207", "GSM63208", "GSM63210", "GSM63211", "GSM63212", "GSM63213", "GSM63214", "GSM63215", "GSM63216", "GSM63217", "GSM63218", "GSM63220"], "sample_count": 14, "group_sizes": null, "group_sizes_basis": null, "platform": "339", "taxon": "Mus musculus", "title": "Gene Expression Profiling of 17 beta-Estradiol and Genistein Effects on Mouse Thymus", "resolution_checked_at": "2026-11-01T15:30:21Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE5145", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5145", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE5145", "version": null, "note": "The Comparative Toxicogenomics Database (CTD) includes manually-curated, cross-species relations between chemicals and genes, proteins, and mRNA transcripts [13]. We downloaded the knowledge-base spanning 4,078 chemicals and 15 461 genes and 85 937 relationships between them in January 2009.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The Comparative Toxicogenomics Database (CTD) includes manually-curated, cross-species relations between chemicals and genes, proteins, and mRNA transcripts [13]. We downloaded the knowledge-base spanning 4,078 chemicals and 15 461 genes and 85 937 relationships between them in January 2009.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM116101", "GSM116102", "GSM116103", "GSM116104", "GSM116105", "GSM116106"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Genes regulated by vitamin D in bronchial smooth muscle cells", "resolution_checked_at": "2026-11-01T15:14:33Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE6883", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6883", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE6883", "version": null, "note": "The Comparative Toxicogenomics Database (CTD) includes manually-curated, cross-species relations between chemicals and genes, proteins, and mRNA transcripts [13]. We downloaded the knowledge-base spanning 4,078 chemicals and 15 461 genes and 85 937 relationships between them in January 2009.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The Comparative Toxicogenomics Database (CTD) includes manually-curated, cross-species relations between chemicals and genes, proteins, and mRNA transcripts [13]. We downloaded the knowledge-base spanning 4,078 chemicals and 15 461 genes and 85 937 relationships between them in January 2009.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM158635", "GSM158636", "GSM158637", "GSM158638", "GSM158639", "GSM158640", "GSM158641", "GSM158642", "GSM158643", "GSM158644", "GSM158645", "GSM158646", "GSM158647", "GSM158648", "GSM158649", "GSM158650", "GSM158651", "GSM158652", "GSM158653", "GSM158654", "GSM158655", "GSM158656", "GSM158657", "GSM158658"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "96;97", "taxon": "Homo sapiens", "title": "The prognostic role of a gene signature from tumorigenic breast-cancer cells.", "resolution_checked_at": "2026-11-01T15:30:21Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE6919", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6919", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE6919", "version": null, "note": "The Comparative Toxicogenomics Database (CTD) includes manually-curated, cross-species relations between chemicals and genes, proteins, and mRNA transcripts [13]. We downloaded the knowledge-base spanning 4,078 chemicals and 15 461 genes and 85 937 relationships between them in January 2009.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The Comparative Toxicogenomics Database (CTD) includes manually-curated, cross-species relations between chemicals and genes, proteins, and mRNA transcripts [13]. We downloaded the knowledge-base spanning 4,078 chemicals and 15 461 genes and 85 937 relationships between them in January 2009.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM152804", "GSM152805", "GSM152806", "GSM152807", "GSM152808", "GSM152809", "GSM152810", "GSM152811", "GSM152812", "GSM152813", "GSM152814", "GSM152815", "GSM152816", "GSM152817", "GSM152818", "GSM152819", "GSM152820", "GSM152821", "GSM152822", "GSM152823", "GSM152824", "GSM152825", "GSM152826", "GSM152827", "GSM152828", "GSM152829", "GSM152830", "GSM152831", "GSM152832", "GSM152833", "GSM152834", "GSM152835", "GSM152836", "GSM152837", "GSM152838", "GSM152839", "GSM152840", "GSM152841", "GSM152842", "GSM152843", "GSM152844", "GSM152845", "GSM152846", "GSM152847", "GSM152848", "GSM152849", "GSM152850", "GSM152851", "GSM152852", "GSM152853", "GSM152854", "GSM152855", "GSM152856", "GSM152857", "GSM152858", "GSM152859", "GSM152860", "GSM152861", "GSM152862", "GSM152863", 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"GSM153018", "GSM153019", "GSM153020", "GSM153021", "GSM153022", "GSM153023", "GSM153024", "GSM153025", "GSM153026", "GSM153027", "GSM153028", "GSM153029", "GSM153030", "GSM153031", "GSM153032", "GSM153033", "GSM153034", "GSM153035", "GSM153036", "GSM153037", "GSM153038", "GSM153039", "GSM153040", "GSM153041", "GSM153042", "GSM153043", "GSM153044", "GSM153045", "GSM153046", "GSM153047", "GSM153048", "GSM153049", "GSM153050", "GSM153051", "GSM153052", "GSM153053", "GSM153054", "GSM153055", "GSM153056", "GSM153057", "GSM153058", "GSM153059", "GSM153060", "GSM153061", "GSM153062", "GSM153063", "GSM153064", "GSM153065", "GSM153066", "GSM153067", "GSM153068", "GSM153069", "GSM153070", "GSM153071", "GSM153072", "GSM153073", "GSM153074", "GSM153075", "GSM153076", "GSM153077", "GSM153078", "GSM153079", "GSM153080", "GSM153081", "GSM153082", "GSM153083", "GSM153084", "GSM153085", "GSM153086", "GSM153087", "GSM153088", "GSM153089", "GSM153090", "GSM153091", "GSM153092", "GSM153093", "GSM153094", "GSM153095", "GSM153096", "GSM153097", "GSM153098", "GSM153099", "GSM153100", "GSM153101", "GSM153102", "GSM153103", "GSM153104", "GSM153105", "GSM153106", "GSM153107", "GSM153108", "GSM153109", "GSM153110", "GSM153111", "GSM153112", "GSM153113", "GSM153114", "GSM153115", "GSM153116", "GSM153117", "GSM153118", "GSM153119", "GSM153120", "GSM153121", "GSM153122", "GSM153123", "GSM153124", "GSM153125", "GSM153126", "GSM153127", "GSM153128", "GSM153129", "GSM153130", "GSM153131", "GSM153132", "GSM153133", "GSM153134", "GSM153135", "GSM153136", "GSM153137", "GSM153138", "GSM153139", "GSM153140", "GSM153141", "GSM153142", "GSM153143", "GSM153144", "GSM153145", "GSM153146", "GSM153147", "GSM153148", "GSM153149", "GSM153150", "GSM153151", "GSM153152", "GSM153153", "GSM153154", "GSM153155", "GSM153156", "GSM153157", "GSM153158", "GSM153159", "GSM153160", "GSM153161", "GSM153162", "GSM153163", "GSM153164", "GSM153165", "GSM153166", "GSM153167", "GSM153168", "GSM153169", "GSM153170", "GSM153171", "GSM153172", "GSM153173", "GSM153174", "GSM153175", "GSM153176", "GSM153177", "GSM153178", "GSM153179", "GSM153180", "GSM153181", "GSM153182", "GSM153183", "GSM153184", "GSM153185", "GSM153186", "GSM153187", "GSM153188", "GSM153189", "GSM153190", "GSM153191", "GSM153192", "GSM153193", "GSM153194", "GSM153195", "GSM153196", "GSM153197", "GSM153198", "GSM153199", "GSM153200", "GSM153201", "GSM153202", "GSM153203", "GSM153204", "GSM153205", "GSM153206", "GSM153207", "GSM153208", "GSM153209", "GSM153210", "GSM153211", "GSM153212", "GSM153213", "GSM153214", "GSM153215", "GSM153216", "GSM153217", "GSM153218", "GSM153219", "GSM153220", "GSM153221", "GSM153222", "GSM153223", "GSM153224", "GSM153225", "GSM153226", "GSM153227", "GSM153228", "GSM153229", "GSM153230", "GSM153231", "GSM153232", "GSM153233", "GSM153234", "GSM153235", "GSM153236", "GSM153237", "GSM153238", "GSM153239", "GSM153240", "GSM153241", "GSM153242", "GSM153243", "GSM153244", "GSM153245", "GSM153246", "GSM153247", "GSM153248", "GSM153249", "GSM153250", "GSM153251", "GSM153252", "GSM153253", "GSM153254", "GSM153255", "GSM153256", "GSM153257", "GSM153258", "GSM153259", "GSM153260", "GSM153261", "GSM153262", "GSM153263", "GSM153264", "GSM153265", "GSM153266", "GSM153267", "GSM153268", "GSM153269", "GSM153270", "GSM153271", "GSM153272", "GSM153273", "GSM153274", "GSM153275", "GSM153276", "GSM153277", "GSM153278", "GSM153279", "GSM153280", "GSM153281", "GSM153282", "GSM153283", "GSM153284", "GSM153285", "GSM153286", "GSM153287", "GSM153288", "GSM153289", "GSM153290", "GSM153291", "GSM153292", "GSM153293", "GSM153294", "GSM153295", "GSM187524", "GSM187525", "GSM187526", "GSM187527", "GSM187528", "GSM187529", "GSM187530", "GSM187531", "GSM187532", "GSM187533", "GSM187534", "GSM187535"], "sample_count": 504, "group_sizes": null, "group_sizes_basis": null, "platform": "93;8300;92", "taxon": "Homo sapiens", "title": "Expression Data from Normal and Prostate Tumor Tissues", "resolution_checked_at": "2026-11-01T15:30:21Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:20459635:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0cef92c1984f87a9139213d0e37217ec44b5bb211b7350e0c428bd48af984a96", "bytes": 1117, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#T1", "version": null, "note": "Chemical Prediction Results from the Verification Phase.", "structure": {"pmcid": "PMC2880288", "section_index": 8, "section_title": "Verification Phase", "row_count": 12, "column_count": 6}, "table": {"label": "Table 1", "caption": "Chemical Prediction Results from the Verification Phase.", "rows": [["Actual Chemical Exposure (GEO accession)", "Chemicals Predicted", "Hypergeometric P-value", "Rank (Percentile)", "q-value", "Relevant Genes Expressed"], ["Vitamin D3 on H. sapiens muscle cells (GSE5145)", "Calcitriol", "1 × 10-23", "1 (100)", "0", "VDR (25), CYP24A1 (14)"], [""], ["TCDD on M. musculus (GSE10082)", "TCDD", "2 × 10-15", "3 (99)", "0", "CYP1A1 (59), CYP1B1 (15), AHRR(6), CYP1A2 (14)"], [""], ["Bisphenol A on H. sapiens Ishikawa cells (GSE17624)", "Bisphenol A", "1 × 10-6", "15 (99)", "0", "ESR1(31), ESR2(7), S100G (6)"], [""], ["Zinc sulfate on H. sapiens bronchial tissue (GSE2111)", "Zinc sulfate", "3 × 10-3", "15 (99)", "0.04", "SLC30A1 (3), MT1F(2), MT1G(2)"], [""], ["Estradiol on M. musculus thymus (GSE2889)", "Estradiol", "5 × 10-3", "17 (99)", "0.08", "C3(6), LPL (4), CTSB (2)"], [""], ["Estradiol on H. sapiens MCF7 cell line (GSE11352)", "Estradiol", "5 × 10-3", "19 (99)", "0.08", "ISG20 (2), MGP (2), SERPINA1 (2)"]], "row_count": 12, "column_count": 6, "numeric_cells": 30, "header_rows": 1, "locator": "section[8]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:20459635:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:eb2fcd632393149a514deec8e5d61ccbbcb59a26f23b18149412b6e5695a7b59", "bytes": 1248, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#T2", "version": null, "note": "Prediction of environmental chemicals associated with prostate cancer samples (GSE6919).", "structure": {"pmcid": "PMC2880288", "section_index": 9, "section_title": "Predicting Environmental Chemicals Associated with Cancer Data Sets", "row_count": 20, "column_count": 6}, "table": {"label": "Table 2", "caption": "Prediction of environmental chemicals associated with prostate cancer samples (GSE6919).", "rows": [["Chemical Predicted", "Hypergeometric P-value", "Rank (percentile)", "q-value", "Relevant genes in set (number of references)", "Citations"], ["Estradiol", "4 × 10-10", "5 (99)", "0", "ESR2(37), PGR(34), MAPK1(14)", "[37]"], [""], ["Raloxifene", "1 × 10-9", "6 (99)", "0", "ESR2(6), IGF1(5), BCL2(4)", "[38]"], [""], ["Sodium arsenite", "1 × 10-8", "8 (99)", "0", "JUN(13), MAPK1(9), CCND1(8), FOS(6)", "[30]"], [""], ["Doxorubicin", "7 × 10-7", "11 (99)", "0", "BCL2(23), MAPK1(14), TNF(10)", "[39-42]"], [""], ["Cadmium", "6 × 10-6", "13 (99)", "0", "MT2A(14), MT1A(12), MT3(11), MT1(6)", "[43]"], [""], ["Genistein", "3 × 10-5", "19 (99)", "6 × 10-4", "ESR2(22), PGR (10), MAPK1 (5)", "[44-46]"], [""], ["Diethylstilbestrol", "3 × 10-5", "22 (98)", "0.001", "ESR2(8), FOS(8), HOXA10(4)", "[47,48]"], [""], ["Fenretinide", "3 × 10-4", "40 (97)", "0.004", "BCL2(3), ELF3(2), LDHA(2)", "[49]"], [""], ["Bisphenol A", "6 × 10-4", "47 (96)", "0.01", "PGR(8), ESR2(7), IL4RA(2)", "[37]"], [""], ["Zinc", "9 × 10-4", "53 (96)", "0.01", "MT3(18), MT2A(13), MT1A(11)", "[50-53]"]], "row_count": 20, "column_count": 6, "numeric_cells": 50, "header_rows": 1, "locator": "section[9]/table-wrap[1]#T2"}}, {"id": 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"CASP3(60), ABCB1(28), BAX(26), BCL2 (23)", "[54]"], [""], ["Sodium arsenite", "8 × 10-6", "20 (98)", "4 × 10-4", "JUN(13), NQ01(6), EGR1(6)", "[55-57]"], [""], ["Vanadium pentoxide", "1 × 10-5", "24 (98)", "6 × 10-4", "HBEGF(3), CDK7(1), CDKN1B (1), CDKN1C(1)", "[58]"], [""], ["Dimethylnitrosamine", "6 × 10-5", "27 (98)", "7 × 10-4", "TGFB1(23), TIMP1(15), PCNA(6)", "[31]"], [""], ["Indomethacin", "2 × 10-4", "34 (97)", "0.002", "BIRC5(3), CDKN1B(2), MMP9(2)", "[59-61]"], [""], ["2-Acetylaminofluorene", "3 × 10-4", "36 (97)", "0.003", "ABCB1(4), ABCG2(4), KRT19(2)", "[62]"], [""], ["Asbestos, Serpentine", "4 × 10-4", "39 (97)", "0.004", "IL6(2), MMP9(2), MMP12(2), PDGFB(2)", "[63]"]], "row_count": 14, "column_count": 6, "numeric_cells": 36, "header_rows": 1, "locator": "section[9]/table-wrap[2]#T3"}}, {"id": "asset:table:pmid:20459635:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": 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